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Genome instability in AZFc region on Y chromosome in leukocytes of fertile and infertile individuals following exposure to gamma radiation

  • Genetics
  • Published:
Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

Men are exposed to various doses of ionizing radiation due to living in regions with high natural background radiation, accidentally, occupationally or for cancer treatment. To study genomic instability of AZFc region to gamma radiation, blood samples from normal, oligozoospermia, and azoospermia individuals were irradiated by a Co-60 source.

Methods

Irradiated cells were kept for 48 h in order to repair initial DNA damages. Real time PCR was performed for three markers (SY 1206, SY 1197, SY 579) for testing copy number variation before and after irradiation. Copy number variations were compared by calculation of cycle threshold comparative method.

Results

Copy number variations of studied markers in AZFc region (microdeletion and duplication) in all samples after exposure to radiation increased with a dose dependent fashion. The frequency of instability was significantly higher in samples from infertile men in comparison with fertile ones (p < 0.001).

Conclusion

No significant difference was seen between the two infertile groups (p > 0.05). This observation might be a possible explanation for induction of azoospermia and oligozoospermia after radiotherapy. Increased frequency of induced microdeletion and duplication in infertile men compared with normal might be attributed to the deficiency in repair systems and the genetic factors involved in incomplete spermatogenesis of infertile men.

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References

  1. Howell SJ, Shalet SM. Spermatogenesis after cancer treatment: damage and recovery. J Natl Canc Inst Monogr. 2005;34:12–7.

    Article  CAS  Google Scholar 

  2. Gagetia GC, Krishnamurthy H. Effect of low doses of gamma-radiation on the steady-state spermatogenesis of mouse: a flow-cytometric study. Mutat Res. 1995;332:97–107.

    Article  Google Scholar 

  3. Ash P. The influence of radiation on fertility in man. Br J Radiol. 1980;53:271–8.

    Article  PubMed  CAS  Google Scholar 

  4. Meirow D, Schenker JG. Cancer and male infertility. Hum Reprod. 1995;10:2017–22.

    PubMed  CAS  Google Scholar 

  5. Kuczyk M, Machtens S, Bokemeyer C, Schultheiss D, Jonas U. Sexual function and fertility after treatment of testicular cancer. Curr Opin Urol. 2000;10:473–7.

    Article  PubMed  CAS  Google Scholar 

  6. Deepali P, Snjay P, Jyoti S, Sebastian PC, Sher A. Genomic instability of the DYZ1 repeat in patient with Y chromosome anomalies and males exposed to natural background radiation. DNA Res. 2006;13:103–9.

    Article  Google Scholar 

  7. Snjay P, Jyoti S, Sebastian PC, Ahamd J, Sher A. Tandem duplication and copy number polymorphism of the SRY gene in patients with sex chromosome anomalies and males exposed to natural background radiation. Mol Hum Reprod. 2006;12:113–21.

    Article  Google Scholar 

  8. Snjay P, Jyoti S, Sebastian PC, Sher A. AZFc somatic microdeletions and copy number polymorphism of the DAZ genes in human males exposed to natural background radiation. Hum Genet. 2007;121:337–46.

    Article  Google Scholar 

  9. Arruda JT, Silva DM, Silva CC, Moura KKVO, da-Cruz AD. Homologous recombination between HERVs causes duplications in the AZFa region of men accidentally exposed to cesium-137 in Goiânia. Genet Mol Res. 2008;7:1063–9.

    Article  PubMed  CAS  Google Scholar 

  10. Arruda JT. Occurrence of mutations in loci linked to Y chromosome in the offspring born to individuals exposed to ionizing radiation. Genet Mol Res. 2009;8:938.

    Article  CAS  Google Scholar 

  11. Reijo R, Algappan RK, Patrizio P, Page DC. Severe oligospermia resulting from deletion of azoospermia factor gene on Y chromosome. Lancet. 1996;347:1290–3.

    Article  PubMed  CAS  Google Scholar 

  12. McElreavey K, Krausz C, Bishop CE. The human Y chromosome and male infertility. Results Probl Cell Differ. 2000;28:2211–32.

    Google Scholar 

  13. Hughes CM, Lewis SE, McKelvey-Martin VJ, Thompson W. A comparison of baseline and induced DNA damage in human spermatozoa from fertile and infertile men, using a modified comet assay. Mol Hum Reprod. 1996;2:613–9.

    Article  PubMed  CAS  Google Scholar 

  14. Pasqualotto FF, Sharma RK, Kobayashi H, Nelson DR, Thomas AJ, Jr-Agarwal A. Oxidative stress in normospermic men undergoing infertility evaluation. J Androl. 2001;22:316–22.

    PubMed  CAS  Google Scholar 

  15. Papachristou F, Simopoulou M, Touloupidis S. DNA damage and chromosomal aberrations in various types of male factor infertility. Fertil Steril. 2008;9:1774–81.

    Article  Google Scholar 

  16. Hall EJ. Radiobiology for the radiologist. 5th ed. New York: Lippincott Williams and Wilkins; 2000.

    Google Scholar 

  17. Mozdarani H, Salimi M. Numerical chromosome abnormalities in 8-cell embryos generated from gamma-irradiated male mice in the absence and presence of vitamin E. Int J Radiat Biol. 2006;82:817–22.

    Article  PubMed  CAS  Google Scholar 

  18. Mozdarani H, Nazari E. Cytogenetic damage in preimplantation mouse embryos generated after paternal and parental gamma-irradiation and the influence of vitamin C. Reproduction. 2009;137:35–43.

    Article  PubMed  CAS  Google Scholar 

  19. Repping S, de-Vries JW, Van-Daalen SK, Korver CM, Leschot NJ, Van-Der-Veen F. The use of sperm HALO-FISH to determine DAZ gene copy number. Mol Hum Reprod. 2003;9:183–8.

    Article  PubMed  CAS  Google Scholar 

  20. De-Vries JW, Hoffer MJV, Repping S, Hoovers JMN, Leschot NJ, Van-Der-Veen F. Reduced copy number of DAZ genes in subfertile and infertile men. Fertil Steril. 2002;77:68–75.

    Article  PubMed  Google Scholar 

  21. Fernandes S, Huellen K, Goncalves J, Dukal H, Zeisler J, Rajpert-De-Meyts E, et al. High frequency of DAZ1/DAZ2 gene deletions in patients with severe oligozoospermia. Mol Hum Reprod. 2002;8:286–98.

    Article  PubMed  CAS  Google Scholar 

  22. Rozé V, Bresson J, Luc-Fellmann F. Quantitative PCR technique for the identification of microrearrangements of the AZFc region. J Assist Reprod Genet. 2007;24:241–8.

    Article  PubMed  Google Scholar 

  23. World Health Organization. WHO manual for the standardized investigation and diagnosis of the infertile couple. Cambridge: Cambridge University Press; 2000.

    Google Scholar 

  24. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) method. Methods. 2001;25:402–8.

    Article  PubMed  CAS  Google Scholar 

  25. Neel JV, Lewis SE. The comparative radiation genetics of humans and mice. Annu Rev Genet. 1990;24:327–62.

    Article  PubMed  CAS  Google Scholar 

  26. Meistrich ML. Male gonadal toxicity. Pediatr Blood Canc. 2009;53:261–6.

    Article  Google Scholar 

  27. Colpi GM, Contalbi GF, Nerva F, Sagone P, Piediferro G. Testicular function following chemo–radiotherapy. Eur J Obstet Gynecol Reprod Biol. 2004;113S:S2–6.

    Article  Google Scholar 

  28. Hermann RM, Henkel K, Christiansen H, Vorwerk H, Hille A. Testicular dose and hormonal changes after radiotherapy of rectal cancer. Radiother Oncol. 2005;75:83–8.

    Article  PubMed  CAS  Google Scholar 

  29. Papachristou F, Lialiaris T, Touloupidis S, Kalaitzis C, Simopoulos C, Sofikitis N. Evidence of increased chromosomal instability in infertile males after exposure to mitomycin C and caffeine. Asian J Androl. 2006;8:199–204.

    Article  PubMed  CAS  Google Scholar 

  30. Yamada K, Fujita K, Quan J, Sekine M, Kashima K, Yahata T, et al. Increased apoptosis of germ cells in patients with AZFc deletions. J Assist Reprod Genet. 2010;27:293–7.

    Article  PubMed  Google Scholar 

  31. Crow JF. The origins, patterns and implications of human spontaneous mutation. Nat Rev Genet. 2000;1:40–7.

    Article  PubMed  CAS  Google Scholar 

  32. Wyman C, Kanaar R. DNA double-strand break repair: all’s well that ends well. Annu Rev Genet. 2006;40:363–83.

    Article  PubMed  CAS  Google Scholar 

  33. Gasior SL, Wakeman TP, Xu B, Deininger PL. The human LINE-1 retrotransposon creates DNA double-strand breaks. J Mol Biol. 2006;357:1383–93.

    Article  PubMed  CAS  Google Scholar 

  34. Mahowald GK, Baron JM, Sleckman BP. Collateral damage from antigen receptor gene diversification. Cell. 2008;135:1009–12.

    Article  PubMed  CAS  Google Scholar 

  35. Nili HA, Mozdarani H, Aleyasin A. Correlation of sperm DNA damage with protamine deficiency in Iranian subfertile men. Reprod BioMedicine Online. 2009;184:479–85.

    Article  Google Scholar 

  36. Falk M, Lukasova E, Kozubek S. Higher-order chromatin structure in DSB induction repair and misrepair. Mutat Res. 2010;704:88–100.

    Article  PubMed  CAS  Google Scholar 

  37. Moskovtsev SI, Mullen JB, Lecker I, Jarvi K, White J, Roberts M. Frequency and severity of sperm DNA damage in patient with confirmed cases of male infertility of different etiology. Reprod BioMedicine Online. 2010;20:759–63.

    Article  CAS  Google Scholar 

  38. Bryant PE. The signal model a possible explanation for the conversion of DNA double strand breaks in to chromatid breaks. Int J Radiat Biol. 1998;73:243–51.

    Article  PubMed  CAS  Google Scholar 

  39. Bryant PE, Mozdarani H. Mechanisms underlying the conversion of DNA double strand breaks in to chromatid breaks. Int J Low Radiat. 2004;1:223–30.

    Article  CAS  Google Scholar 

  40. Sankaranarayanan K, Wassom JS. Ionizing radiation and genetic risks XIV. Potential research directions in the post-genome era based on knowledge of repair of radiation-induced DNA double-strand breaks in mammalian somatic cells and the origin of deletions associated with human genomic disorders. Mutat Res. 2005;578:333–70.

    Article  PubMed  CAS  Google Scholar 

  41. Baker S, Plug A, Prolla T, Bronner C, Harris A, Yao X, et al. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over. Nat Genet. 1996;13:336–42.

    Article  PubMed  CAS  Google Scholar 

  42. Mark S, Renee A, Reijo P. Male infertility, genetic analysis of the DAZ on Y chromosome and genetic analysis of DNA repair. Mol Cell Endocrinol. 2001;184:41–9.

    Article  Google Scholar 

Download references

Acknowledgements

This work was supported by Research Department of the Faculty of Medical Sciences of Tarbiat Modares University, Tehran, Iran. The authors wish to express their sincere thanks to all patients and healthy individuals for their blood donation and kind contribution and Ms Zahra Tizmaghz for irradiation of samples.

Conflict of Interest statement

The authors declare that there are no conflicts of interest.

Author information

Authors and Affiliations

  1. Department of Medical Genetics, Faculty of Medical Sciences, Tarbiat Modares University, P.O.Box: 14115–111, Tehran, Iran

    Sahar Moghbeli-Nejad & Hossein Mozdarani

  2. Department of Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

    Mehrdad Behmanesh

  3. Department of Infertility, Shariati Hospital, Tehran, Iran

    Zahra Rezaiean & Parvin Fallahi

Authors
  1. Sahar Moghbeli-Nejad
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  2. Hossein Mozdarani
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  3. Mehrdad Behmanesh
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  4. Zahra Rezaiean
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  5. Parvin Fallahi
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Corresponding author

Correspondence to Hossein Mozdarani.

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Capsule

Lymphocytes from infertile individuals showed higher frequency of genome instability in AZFc region on Y chromosome after gamma irradiation compared to normal controls.

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Moghbeli-Nejad, S., Mozdarani, H., Behmanesh, M. et al. Genome instability in AZFc region on Y chromosome in leukocytes of fertile and infertile individuals following exposure to gamma radiation. J Assist Reprod Genet 29, 53–61 (2012). https://doi.org/10.1007/s10815-011-9626-5

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  • DOI: https://doi.org/10.1007/s10815-011-9626-5

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